Varenicline for the treatment of cocaine dependence: A phase II clinical trial. Cocaine dependence remains a major public health problem, even after over two decades of steady attempts to develop effective behavioral and pharmacological interventions for treating cocaine dependence. Due to the health costs that come directly from cocaine use (e.g., coronary and vascular problems), and those that are more indirect (e.g., spread of AIDS, HCV from exchanging sex for drugs), it is imperative that efforts to develop efficacious treatments continue. To that end, this is a proposed double-blind placebo-controlled clinical trial (n = 200) of varenicline for the treatment of cocaine dependence that utilizes contingency management to promote treatment attendance. In a recently completed pilot trial (n = 37) using the same design, we found that subjects randomized to varenicline showed greater decreases in cocaine use as well as reductions in how valuable or reinforcing they found cocaine (Plebani et al., revision under review). In that study, we used a variable schedule of reinforcement to promote high rates of attendance. That reinforcement led to dramatic increases in attendance rates, and led to far less missing data than usually plagues such trials. Due to these promising results, we now seek to replicate that study in a larger sample in order to have the power to more fully determine the efficacy of varenicline as a treatment for cocaine dependence. PUBLIC HEALTH RELEVANCE: Cocaine dependence is a major public health problem, with few effective treatments, high relapse rates, and a strong association with negative health consequences. As such, research examining potential cocaine dependence medications is needed. Such research should utilize behavioral intervention to maximize treatment attendance and retention in order to better determine medication efficacy, and thus decrease the burden that cocaine dependence places on the healthcare system and on society.